In response: Hyperuricemia as a risk factor for cardiovascular disease

Response to: Katsiki N, Doumas M, Athyros VG, Karagiannis A. Hyperuricemia as a risk factor for cardiovascular disease. Expert Rev Cardiovasc Ther 2015;13(1):19-20

Dear Editor,

We are grateful to Katsiki et al. for their interest for our review focused on the relationship between serum uric acid (SUA) level and risk of cardiovascular disease [1,2]. Of course, we agree with the concept that the positive and negative interaction between largely prescribed drugs and SUA is more complex that previously suggested. We also agree that hyperuricemia is not only directly related to cardiovascular disease risk, but also to pathophysiological conditions associated to increased cardiovascular risk such as nonalcoholic fatty liver disease and chronic kidney disease. All these observations confirm the role of SUA as a marker of systemic oxidative stress, per se involved in the pathogenesis of a large number of clinical conditions. In agreement with this hypothesis, we recently also published data that relates SUA level with the ones of other markers of systemic oxidative stress related to cardiovascular disease, the serum level of oxidized low density lipoproteins (LDL) and dienes, in a relatively large sample of overall healthy adult-elderly men and women [3]. Similar results have been previously observed by Barbosa et al. [4] in a smaller sample of younger subjects and by Ruíz-Hernández et al. [5]., who limited their study on overweight women. We also observed that SUA was associated with the dienes level, but not with the LDL lag phase and propagation phase length. The formation of conjugated dienes is an early event of lipid peroxidation taking place soon after the initiation of the chain reaction [6], and the oxidation-induced increase of diene conjugation in LDL lipids is well documented [7]. In vitro, Patterson et al. demonstrated that UA rapidly reduces Cu2+ to Cu+, and the decreased concentration of Cu2+ would inhibit tocopherol-mediated peroxidation in native LDL, while the generation of Cu+ would promote the rapid breakdown of lipid hydroperoxides in mildly oxidized LDL into lipid radicals [8]. The explication of our result could be that high SUA level promotes oxidative stress trough the generation of free oxygen radicals, thus inducing an increase in circulating ox-LDL, or is more simply an indirect marker of systemic oxidation or exposition to oxidative stress, but probably does not directly affect the LDL resistance to oxidation. Therefore, it could be argued, but it is yet to be proven, that the inhibition of xanthine oxidase could improve the level of systemic oxidative stress and consequently also the level of circulating ox-LDL, with the resulting positive effects on the health of arterial walls and prevention of hypertension development.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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